Evidence map›Paper›PMID 26566947›Full record

ArticleG3 (Bethesda, Md.)2015

Identification of a Classical Mutant in the Industrial Host Aspergillus niger by Systems Genetics: LaeA Is Required for Citric Acid Production and Regulates the Formation of Some Secondary Metabolites.

Jing Niu, Mark Arentshorst, P Deepa S Nair, Ziyu Dai, Scott E Baker, Jens C Frisvad, Kristian F Nielsen, Peter J Punt, Arthur F J Ram

Open access · goldAbstract read
In one paragraph

Article in G3 (Bethesda, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Review
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  4. Engineering of Global Transcriptional Regulators (GTRs) inJournal of fungi (Basel, Switzerland) · 2025
    Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Itaconic acid production is regulated by LaeA inMetabolic engineering communications · 2022
    Article
  17. Article
  18. Review
  19. Article
  20. Deletion of theMicroorganisms · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Jing NiuMolecular Microbiology and Biotechnology, Institute of Biology Leiden, Leiden University, 2333 BE, Leiden, The Netherlands.
Mark ArentshorstMolecular Microbiology and Biotechnology, Institute of Biology Leiden, Leiden University, 2333 BE, Leiden, The Netherlands.
P Deepa S NairMolecular Microbiology and Biotechnology, Institute of Biology Leiden, Leiden University, 2333 BE, Leiden, The Netherlands.
Ziyu DaiChemical and Biological Process Development Group, Pacific Northwest National Laboratory, Richland, Washington 99352.
Scott E BakerEnvironmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352.
Jens C FrisvadDepartment of Systems Biology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark.
Kristian F NielsenDepartment of Systems Biology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark.
Peter J PuntMolecular Microbiology and Biotechnology, Institute of Biology Leiden, Leiden University, 2333 BE, Leiden, The Netherlands Dutch DNA, 3700 AJ Zeist, The Netherlands.
Arthur F J RamMolecular Microbiology and Biotechnology, Institute of Biology Leiden, Leiden University, 2333 BE, Leiden, The Netherlands a.f.j.ram@biology.leidenuniv.nl.
Leiden University · NLPacific Northwest National Laboratory · USTechnical University of Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The asexual filamentous fungus Aspergillus niger is an important industrial cell factory for citric acid production. In this study, we genetically characterized a UV-generated A. niger mutant that was originally isolated as a nonacidifying mutant, which is a desirable trait for industrial enzyme production. Physiological analysis showed that this mutant did not secrete large amounts of citric acid and oxalic acid, thus explaining the nonacidifying phenotype. As traditional complementation approaches to characterize the mutant genotype were unsuccessful, we used bulk segregant analysis in combination with high-throughput genome sequencing to identify the mutation responsible for the nonacidifying phenotype. Since A. niger has no sexual cycle, parasexual genetics was used to generate haploid segregants derived from diploids by loss of whole chromosomes. We found that the nonacidifying phenotype was caused by a point mutation in the laeA gene. LaeA encodes a putative methyltransferase-domain protein, which we show here to be required for citric acid production in an A. niger lab strain (N402) and in other citric acid production strains. The unexpected link between LaeA and citric acid production could provide new insights into the transcriptional control mechanisms related to citric acid production in A. niger. Interestingly, the secondary metabolite profile of a ΔlaeA strain differed from the wild-type strain, showing both decreased and increased metabolite levels, indicating that LaeA is also involved in regulating the production of secondary metabolites. Finally, we show that our systems genetics approach is a powerful tool to identify trait mutations.

Indexed as

Genes, FungalAllelesAspergillus nigerCitric AcidGenetic Complementation TestGenotypeMutationPhenotypePolymorphism, Single NucleotideSecondary MetabolismCitric Acidbulk segregant analysisfilamentous fungigenome sequencingorganic acidsparasexual cycle

Identifiers

PMID26566947
PMCPMC4704718
OpenAlexW2207182837

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.